PROJECT SUMMARY In recent years, strong evidence has accrued indicating that inflammation (INF) and metabolic syndrome (MS) represent dysregulated biological systems that predict onset of chronic, age-related diseases such as cardiovascular disease, type 2 diabetes, rheumatoid arthritis, cancer, and dementia. Although a wealth of findings has indicated that psychosocial stress is a major determinant of INF and MS, a number of crucial questions remain unanswered. First, we do not know whether sensitive period (early biological programming), stress accumulation, social schematic, or mismatch models best account for the development of INF and MS. Second, we have little information regarding the range of stressors within a developmental period that are most critical. Studies of childhood stress usually simply assess low SES or exposure to harsh parenting, and these measurements typically entail retrospective reports. Research on the effect of adult stress sometimes includes community context but usually fails to consider the way that childhood stress may moderate reactions to adult stressors. And, whether the focus is childhood or adult adversity, there has been limited consideration of the way that race-related stressors such as segregation, perceived racism, discrimination, and internalized racism impact biological dysregulation. Third, we know little about the extent to which factors such as parental support, racial socialization, social support, or religiosity operate to reduce the deleterious impact of childhood, adolescent, or adult stressors on INF and MS. A final limitation of past research is that it has focused, with a few exceptions, on White samples whereas African Americans display significantly higher rates of almost every type of chronic illness and score higher on biomarkers of INF and most indictors of MS. In order to address these unanswered questions and limitations, this proposal seeks funding to add biomarkers of INF and MS, as well as telephone interview data regarding stress and health behaviors, to the 18 years of longitudinal data that has been collected on the Family and Community Health Study (FACHS) sample of roughly 700 African Americans (now 28 years of age). Specifically, we plan to pursue the following specific aims: 1) identify the cluster of SES- and race-related stressors experienced in childhood, adolescence, and adulthood that best predict adult INF and MS. 2) Use these stress indices to test competing models regarding the manner in which stressors from various developmental periods combine to influence biological dysregulaton. And, 3) investigate the extent to which the experience of supportive parenting and racial socialization during childhood, and/or supportive relationships and religiosity during adulthood, are moderating factors that promote healthy biomarkers for INF and MS. There are few, if any, efficacious preventive interventions that address the causes of health disparities. The Institute of Medicine prescribes that such efforts be based on the results of longitudinal, epidemiological research with target populations. Currently, there are no prospective investigations that identify the protective factors that interrupt the translation of social determinants of stress into biological vulnerabilities for African Americans. The results of the proposed research will identify protective processes and serve as the basis for empirically-based, health disparities preventive interventions.